To test a script containing SMILES codes of diketopiperazines that are available to order from NCHLabs and see if any will dock via THINK.
Procedure
Started THINK and opened up the enzyme file. Went to File>PReferences>Pharmacophores and set Warp speed equal to 1, and Configure for equal to 2 centers. Next Went to Search>3D and made sure the query was set to the enzyme and browsed for the sdf script file. Set tolerance = 1. Allowed THINK to run until 150 molecules were tested.
Results
Approximate time of run was 48-54 hours. 79 diketopiperazines were found to be hits out of the 151 that were tested which is 151 out of a total of 234 in the sdf file under the conditions stated in the procedure. This excel sheet has the delta G values and what diketopiperazine they go to. Looking at the docked diketopiperazines in THINK, the majority of them bond at one of the amide carbonyls on the piperazine ring and a methoxy group if present. For example NCHLabs234#2 However NCHLabs234#15 seems to bond twice to the same methoxy group. Do we have any pics of pdb files of docking with 2 centers?
Discussion
More information has to be obtained about the tolerance condition as well as the number of centers. Some information can be found from D-EXP002 It seems that the tolerance values based on the results from D-EXP002 would suggest that if a molecule is given more "wiggle" room (conditions that would mimic those of the conditions of coming in contact with the enzyme) then the diketopiperazines would probably dock in some percentage that would be relative to the conditions of the enzyme. Also from D-EXP002, the centers seem to correspond to the receptor sites of the diketopiperazine and not the enzyme. For example, those diketopiperazines that do not have 4 possible active bonding sites, there is no hit value. The sdf file that was run in this file was run with 3 and 4 centers and results were reported within seconds that there are no hits.
Conclusion
None of these molecules dock with 4 centers and a tolerance of 1, conditions where all 5 sample molecules in D-EXP002 dock.
Objective
To test a script containing SMILES codes of diketopiperazines that are available to order from NCHLabs and see if any will dock via THINK.Procedure
Started THINK and opened up the enzyme file. Went to File>PReferences>Pharmacophores and set Warp speed equal to 1, and Configure for equal to 2 centers. Next Went to Search>3D and made sure the query was set to the enzyme and browsed for the sdf script file. Set tolerance = 1. Allowed THINK to run until 150 molecules were tested.Results
Approximate time of run was 48-54 hours.79 diketopiperazines were found to be hits out of the 151 that were tested which is 151 out of a total of 234 in the sdf file under the conditions stated in the procedure. This excel sheet has the delta G values and what diketopiperazine they go to. Looking at the docked diketopiperazines in THINK, the majority of them bond at one of the amide carbonyls on the piperazine ring and a methoxy group if present. For example NCHLabs234#2 However NCHLabs234#15 seems to bond twice to the same methoxy group.
Do we have any pics of pdb files of docking with 2 centers?
Discussion
More information has to be obtained about the tolerance condition as well as the number of centers. Some information can be found from D-EXP002 It seems that the tolerance values based on the results from D-EXP002 would suggest that if a molecule is given more "wiggle" room (conditions that would mimic those of the conditions of coming in contact with the enzyme) then the diketopiperazines would probably dock in some percentage that would be relative to the conditions of the enzyme. Also from D-EXP002, the centers seem to correspond to the receptor sites of the diketopiperazine and not the enzyme. For example, those diketopiperazines that do not have 4 possible active bonding sites, there is no hit value. The sdf file that was run in this file was run with 3 and 4 centers and results were reported within seconds that there are no hits.Conclusion
None of these molecules dock with 4 centers and a tolerance of 1, conditions where all 5 sample molecules in D-EXP002 dock.